System for evaluation of inter-instrument difference

This application claims priority from prior European Patent Applications No. 24221535.8, filed on Dec. 19, 2024, and No. 24221538.2, filed on Dec. 19, 2024, the entire contents of which are incorporated herein by reference.

The present disclosure relates to a sample analysis system and corresponding computer program. In particular, the present disclosure relates to a sample analysis system and corresponding computer program for evaluating an inter-instrument difference, that is, evaluating measurement differences among measurement units measuring a same sample.

If more than one sample measurement unit is installed at a facility, it may be required to be able to obtain equivalent measurement results by each of the sample measurement units when the same sample is measured by each of the sample measurement units for a same measurement item. In facilities where multiple sample measurement units are installed, in order to confirm the equivalence of measurement results by each sample measurement unit (inter-instrument difference evaluation) on a regular basis, the same sample is measured by each of target sample measurement units that are subject to the inter-instrument difference evaluation and measurement results are compared among the target sample measurement units.

, Development and Validation of Effective Real Time and Periodic Interinstrument Comparison Method for Automatic Hematology Analyzers Conventionally, for example according to S. Park, et al. (December, 2014). Am J Clin Pathol 2014; 142:777-787-, when performing the inter-instrument difference evaluation, operator involvement has been significantly required. Hence, there is a problem that a huge burden is placed on the operator. There is thus a need to reduce the burden of the operator when performing the inter-instrument difference evaluation.

According to an aspect of the present disclosure, a sample analysis system comprises: a plurality of measurement units, each configured to measure a sample to obtain a measurement result based on a measurement order including one or more measurement items; an identification information reader configured to read identification information of each of a plurality of samples to be measured by at least one of the plurality of measurement units; and a computer that communicates with the identification information reader and the plurality of measurement units, and comprises a storage device configured to store the measurement results. Each of the plurality of samples is measured for diagnosis of a test subject by at least one of the plurality of measurement units based on the measurement order, and a measurement result of the measured sample obtained from the at least one of the plurality of measurement units is stored in the storage device in association with the identification information of the measured sample. A plurality of target measurement units designated from the plurality of measurement units are subject for inter-instrument difference evaluation, and at least one of the plurality of samples is measured by each of the plurality of target measurement units based on the measurement order including one or more preset measurement items for the inter-instrument difference evaluation, and a plurality of measurement results of the measured sample obtained from the plurality of target measurement units are stored in the storage device in association with the identification information of the measured sample. The computer is configured to perform operations for the inter-instrument difference evaluation, the operations comprising: interrogating the storage device to identify a set of the plurality of measurement results obtained from the plurality of target measurement units, the set of the plurality of measurement results matching a condition for use in the inter-instrument difference evaluation; and generating evaluation information for the inter-instrument difference evaluation based on the set of the plurality of measurement results identified from the storage device.

160 According to another aspect, a computer program product comprises instructions which cause a computer to carry out operations for inter-instrument difference evaluation, wherein the computer is in communication with: a plurality of measurement units (), each configured to measure a sample to obtain a measurement result based on a measurement order including one or more measurement items; and an identification information reader configured to read identification information of each of a plurality of samples to be measured by at least one of the plurality of measurement units. Each of the plurality of samples is measured for diagnosis of a test subject by at least one of the plurality of measurement units based on the measurement order, and a measurement result of the measured sample obtained from the at least one of the plurality of measurement units is stored in the storage device in association with the identification information of the measured sample. A plurality of target measurement units designated from the plurality of measurement units are subject for inter-instrument difference evaluation, and at least one of the plurality of samples is measured by each of the plurality of target measurement units based on the measurement order including one or more preset measurement items for the inter-instrument difference evaluation, and a plurality of measurement results of the measured sample obtained from the plurality of target measurement units are stored in the storage device in association with the identification information of the measured sample. The operations for the inter-instrument difference evaluation comprise: interrogating the storage device to identify a set of the plurality of measurement results obtained from the plurality of target measurement units, the set of the plurality of measurement results matching a condition for use in the inter-instrument difference evaluation; and generating evaluation information for the inter-instrument difference evaluation based on the set of the plurality of measurement results identified from the storage device.

The present disclosure is related to a sample analysis system for simplifying the inter-instrument difference evaluation. Inter-instrument difference evaluation is to evaluate difference among measurement results obtained from a plurality of different measurement units when each of the measurement units measures a same sample (a target sample). In a situation where multiple measurement units may be used in an operator's site such as a hospital or a laboratory, the inter-instrument difference evaluation is used to ensure accurate and compatible measurements among the multiple measurement units. The inter-instrument difference evaluation may also be used to initiate or trigger an appropriate action if the inter-instrument difference evaluation shows that a measurement result of at least one measurement unit deviates from those of other measurement unit(s) beyond an allowable range. For example, the appropriate action may be an initiation of a cleaning operation, a suspension of the suspicious measurement unit (and a corresponding re-routing of samples to other measurement unit), and the like.

1 4 FIGS.- 1 FIG. 2 FIG. 2 FIG. 100 110 150 150 1 3 110 100 150 110 110 110 111 112 113 114 117 118 119 120 114 115 116 150 113 110 150 113 150 150 As shown in, a sample analysis systemaccording to the present disclosure includes a computation deviceand multiple analyzers. Whileshows three analyzers(analyzers-), this is a non-limiting example of a sample analysis system. A computation device(referred to as computer below, for brevity) may be a machine capable of performing calculation and processing data, and may be a personal computer, an embedded computation device, a mobile device such as a smart phone and a tablet, a server or the like. The sample analysis systemmay be arranged in an operator's site. Alternatively, the analyzersmay be arranged in the operator's site and may be connected with the computerremotely accessible from the operator's site. For example, the computerremotely accessible from the operator's site may be a computer in a cloud infrastructure. As shown in, the computermay include a processor, a memory, a communication device, a storage device, an interfaceconnecting a displayand/or an operation deviceto a communication bus. The storage devicemay include a programfor executing the inter-instrument difference evaluation as described below, and a databasefor storing measurement results obtained by at least one of the analyzers. Whileshows, for illustrative purposes, a communication line (which may be a wired or wireless communication line) between the communication deviceof the computerand an analyzer, the skilled person understands that the communication devicemay be communicatively connected with more than one analyzerand may suitably be configured to receive and transmit data simultaneously or sequentially to these analyzers.

150 150 Each of the multiple analyzersmay be configured to perform a measurement on a biological sample. The measurement result may be utilized by doctors or clinical laboratory operators. For example, based on the measurement result, the doctor may diagnose a patient and determine a medical treatment. For example, the analyzermay be a hematology analyzer (blood cell analyzer), a urine analyzer, a coagulation analyzer, etc. The operator's site may have various types of analyzers. For example, the operator's site may have a plurality of hematology analyzers and a plurality of urine analyzers. However, the inter-instrument difference is evaluated among a same type of analyzers (i.e., the inter-instrument difference among hematology analyzers is evaluated only within a group of hematology analyzers). The same type of analyzers may refer to analyzers that measure samples using a same measurement principle and same type of reagents.

3 FIG. 3 FIG. 1 FIG. 150 160 180 160 180 160 180 160 180 180 110 110 180 160 As shown in, each analyzermay include a measurement unitand a data analysis unit. Whileshows the measurement unitand the data analysis unitas being two different hardware entities, the skilled person understands that the measurement unitand the data analysis unitmay also be embedded or integrated into a single entity. The measurement unitmay measure a biological sample and may transmit measurement data to the data analysis unitwhich may process the measurement data to generate measurement result. The data analysis unitmay be connected to the computer, as shown in, and the generated measurement result may be transmitted to the computerfrom the data analysis unit. The multiple measurement unitsin the sample analysis system may be configured to perform optical and/or electrical measurements. The present disclosure may be applied to any sample analysis system in which a measurement for one or more measurement items of the sample are commonly performed among the multiple measurement units. For example, the multiple measurement units may be a same type of measurement units that perform a measurement of blood cells using flow-cytometry for one or more measurement items that are common among the measurement units. For example, the multiple measurement units may be a same type of measurement units that perform morphological analysis for digital morphological image.

4 FIG. 3 FIG. 150 150 180 160 180 160 180 181 182 183 184 185 186 187 181 182 183 184 187 189 160 161 180 162 163 164 165 163 160 164 162 180 161 180 110 shows an example of a configuration of the analyzer. The analyzermay have the data analysis unitand the measurement unit, as described in. As discussed, the data analysis unitand the measurement unitmay be embedded in a same entity or may be associated with two different entities. The data analysis unitmay include a processor, a memory, a storage device, an interfacefor a displayand an operation device, and a communication device. The processor, the memory, the storage device, the interface, and the communication deviceinteract via a bus. The measurement unitmay be configured with a controllerthat interacts, preferably based on instructions received from the data analysis unit, with other parts including, for example one or more detectors, a sample aspiration section, a sample preparation section, an identification information (ID) reader, such as a barcode reader, or the like. The sample aspiration sectionaspirates a sample from a sample container into the measurement unitthrough a sample nozzle. The sample preparation sectionprepares a measurement sample by mixing a portion (aliquot) of the aspirated sample and at least one reagent such as a diluting solution, a lysing solution or a staining solution in a chamber. As discussed, the one or more detectorsperform measurements on the measurement sample to acquire measurement data which may be transferred to the data analysis unitvia the controller. The data analysis unitmay then generate measurement results from the measurement data. These measurement results may also be displayed, manipulated, edited, filtered, or otherwise processed through interaction via the human-machine interface, and subsequently sent to the computeralong with associated sample information such as sample identification information.

5 FIG.A 1 FIG. 5 FIG.A 110 110 111 115 1 110 110 110 160 100 160 110 110 110 110 160 shows a process to store multiple measurement results of the target sample. The process may be performed by the computerof, in particular by the computerequipped with the processorexecuting corresponding instructions as defined in the computer program. In step Sof, the computermay automatically identify the target sample from a plurality of samples to be measured. The target sample is to be used for a measurement for inter-instrument difference evaluation. The sample other than the target sample is to be used for a measurement to acquire the measurement result for diagnosing and determining the medical treatment. The computermay identify, from a plurality of first samples to be measured for diagnosing and determining the medical treatment, a second sample (the target sample) used for measurement for the evaluation of inter-instrument difference. The target measurement units are subject for the inter-instrument difference evaluation. The computermay identify all measurement unitsinstalled in the sample analysis systemas the target measurement units or may identify some or a subset of the measurement unitsas the target measurement units. The target measurement units may be designated by the operator. The first samples may be used for diagnosing and determining the medical treatment. The second sample (the target sample) identified from the first samples may be used for the inter-instrument difference evaluation, and may also be used for diagnosing and determining the medical treatment. As the target sample, a biological sample such as a blood sample collected from a test subject (e.g., patient) may be used. The computermay identify the target sample based on an ID associated with the sample (e.g., the ID of the first sample). Among the IDs of the first samples, at least one of the ID may be designated as the ID of the target sample. For example, the operator may designate the first sample to be used for the inter-instrument difference evaluation, and set the ID of the designated first sample into the computer. For example, the computermay monitor the IDs of the first samples and determine if the monitored ID matches with the ID of the designated first sample. If the monitored ID matches with the ID of the designated first sample, the computeridentifies the first sample with the matched ID as the target sample. The skilled person understands that the target sample can be used for inter-instrument difference evaluation by evaluating a difference in measurement data or measurement results of the target sample measured by different target measurement units.

110 110 110 110 160 110 110 Instead of a sample collected from the test subject, a quality control sample which is prepared with known quantities of specific analytes may be utilized as the target sample. Conversely, in a facility that prefers the sample collected from the test subject to the quality control sample for the measurement for the inter-instrument difference evaluation, the computermay perform a process to exclude the quality control sample from being identified as the target sample. For example, the computermay distinguish the quality control sample from samples collected from the test subjects, based on the ID corresponding to the quality control sample. For example, the operator may set the IDs corresponding to the quality control samples into the computer. The computermay compare these set IDs (i.e., the IDs of the quality control samples) with the IDs read from the containers of the samples to be measured by the measurement unit. For example, if the read ID matches with the set ID, the computermay determine that the sample is the quality control sample and may not identify it as the target sample. As another example, the quality control sample may have the ID in a predetermined format which is different from an ID format of other samples. The computer, for example, may identify the quality control sample if the read ID has the predetermined format, and then exclude it from being identified as the target sample.

110 110 110 110 The computermay identify the target sample at random. For example, the computermay generate a random number each time when the computeracquires the ID associated with the first sample. If the generated random number matches a predetermined number, the computermay identify the corresponding sample as the target sample.

110 110 110 110 100 110 The computermay identify the target sample based on a predetermined frequency. For example, the computermay identify the target sample per a predetermined number of measurements. The computer, for example, may designate at least one sample as the target sample in every 1000 samples (e.g., the computermay designate at least one sample as the target sample each time 1000 measurements are done in the sample analysis system). For example, the computermay identify the target sample per predetermined interval (e.g., per 8 hours, per a week, etc).

110 160 110 160 110 110 160 160 The computermay identify the target measurement unitsbased on a preset rule. The preset rule may be configured in the computer. The preset rule, for example, may be (i) predetermined group(s) of a plurality of measurement units, and (ii) for the predetermined group(s), predetermined timing/cycle of the inter-instrument difference evaluation. For example, the computermay identify the predetermined group(s) to which the predetermined timing/cycle comes, then the computermay designate the measurement unitsof the identified group(s) as the target measurement units.

The measurement result of the target sample (i.e., the second sample) may be used for the inter-instrument difference evaluation, and also be used for the diagnosis of the test subject (i.e., patient). That is, the measurement result of the target sample may serve both the patient diagnosis and the inter-instrument difference evaluation. For example, if one or more measurement items used in the inter-instrument difference evaluation cover measurement items required for diagnosis of the test subject, the measurement of the target sample for diagnosis of the test subject may be omitted.

2 160 160 160 5 FIG.A In step Sof, each of the target measurement unitsmay conduct a same measurement of the target sample for one or more measurement items (e.g., measurement parameters) for the evaluation of inter-instrument difference. In other words, each of the plurality of target measurement unitsmay measure the second sample based on a measurement order including one or more preset measurement items for the inter-instrument difference evaluation, with these measurement items being common or the same among the target measurement units.

110 160 1 3 1 3 160 110 1 3 1 FIG. The computermay generate the measurement order including the one or more measurement items which have been set for the measurement for the inter-instrument difference evaluation and transmit the generated measurement order to each of the target measurement units. As will also be further detailed below, the measurement items may be set by the operator, for example, via a graphical user interface. In one exemplified case where the measurement units M-Mof corresponding analyzers-inare the target measurement units, the computermay send the measurement order to each of the measurement units M-Mto measure the target sample for the same measurement items for the evaluation of inter-instrument difference.

1 3 110 3 114 116 110 110 160 114 5 FIG.A After the measurement by each of the target measurement units M-M, measurement results may be sent to the computer, and in step Sof, the measurement results of the target sample may be stored in the storage device(database) of the computerin association with ID of the target sample for use in the inter-instrument difference evaluation. In other words, the computermay store a plurality of measurement results of the second sample obtained by measurements by the plurality of measurement unitsin the storage devicefor use in the inter-instrument difference evaluation.

1 110 3 110 5 FIG.A In step Sof, the computermay identify a plurality of second samples (two or more target samples) from the plurality of first samples, and in step S, the computermay, for each of the identified second samples, store the plurality of measurement results of the second sample in the storage device for use in the inter-instrument difference evaluation. Here, the IDs for each of the identified second samples are mutually different from each other.

5 FIG.B 160 100 160 110 110 160 164 160 160 162 160 illustrates an exemplary concept of identifying the target sample and performing measurement of the target sample by each of the target measurement units. The sample analysis systemroutinely receives a plurality of samples (i.e., the first samples) which are to be measured by at least one of the measurement units. These samples (i.e., the first samples) may be used for measurement for diagnosis of the test subjects such as patients. When the computerdetermines that a timing to conduct the inter-instrument difference evaluation has arrived, at least one sample (i.e., the first sample) may be automatically identified as the target sample (i.e., the second sample) by the computerand the target sample may be automatically measured by each of the target measurement unitsfor the inter-instrument difference evaluation. The target sample may be aspirated using the sample aspiration sectionby each of the target measurement unitsfrom the sample container which contains the target sample, that is, a portion of the same target sample may be aspirated by each of the target measurement units, and the aspirated sample is measured by the detector(s)for one or more (same or common) measurement items by each of the target measurement units.

160 160 160 1 2 3 5 FIG.B The one or more measurement items include at least one measurement item that is common among the target measurement units. All measurement items may be common among the target measurement units, or measurement items may be partially overlapped among the target measurement units. For example, as illustrated in, each of the measurement units M, M, Mmay measure the target sample for the same measurement items a, b, c. The skilled person understands that the inter-instrument difference may then be evaluated by comparing measurement results obtained from these measurements.

160 The plurality of the target measurement unitsmay comprise at least a first measurement unit and a second measurement unit. Both of the first and second measurement units may be designated as the target measurement units, and measure the second sample which is designated as the target sample. Here, the first measurement unit may aspirate a portion of the second sample, which is the same sample measured/to be measured by the second measurement unit, from a sample container containing the second sample and measure the aspirated second sample for the one or more measurement items for the inter-instrument difference evaluation, and the second measurement unit may aspirate a portion of the second sample, which is the same sample measured/to be measured by the first measurement unit, from the sample container and measure the aspirated second sample for the one or more measurement items for the inter-instrument difference evaluation.

5 FIG.C 8 FIG. 8 FIG. 8 FIG. 5 FIG.C 5 FIG.C 110 110 110 116 11 110 110 116 160 165 160 110 160 110 165 160 110 110 110 160 110 160 100 110 110 110 160 110 160 160 11 160 1 2 3 160 1 2 3 In one exemplified case, as shown in, the computermay receive operator's designation of the target measurement units, target samples and one or more measurement items for the inter-instrument difference evaluation. If the computerhas received a designation of the target sample, the computermay store, in the databaseas shown in, flag information indicating the inter-instrument difference evaluation in association with the ID (as shown “” in) of the designated target sample. If the computerautonomously designates the target sample, the computermay store, in the databaseas shown in the, the flag information in association with the ID of the designated target sample. When a plurality of sample containers are supplied one by one to at least one of the measurement unitsby the operator or a sample transport device, the ID attached to each supplied sample container may be read by ID reader (identification information reader) of the sample analysis system. For example, the ID readersuch as a barcode reader, located at each measurement unitmay be utilized for reading the ID. The ID read by the ID reader may then be transmitted to the computer. Along with the ID of the sample, the ID of the measurement unit(Instrument ID), which measures the sample corresponding to the ID of the sample, may also be transmitted to the computer. For example, when the ID of the sample is read by the ID reader, the measurement unitmay transmit both the ID of the sample and the Instrument ID to the computer. The computermay determine whether the sample is the target sample to be measured by the target measurement unit based on comparison of the ID read by the ID reader and the ID of the designated target sample. The computermay compare the Instrument ID sent from the measurement unitand the designated Instrument ID as shown in, and, if these IDs are matched (i.e., the measurement unit is recognized as the target measurement unit), the computermay send the measurement order for the inter-instrument difference evaluation to the measurement unit. In other words, the identification information reader of the sample analysis systemmay read IDs of first samples, and the computermay identify the second sample (target sample) from a plurality of the first samples whose IDs have been read by the identification information reader. When the computerhas identified the target sample, the computermay send the measurement order to instruct the target measurement unitto measure the target sample for one or more measurement items which have been set for the inter-instrument difference evaluation. As illustrated in, setting for inter-instrument difference evaluation may be achieved via a graphical user interface, for example, at the computer, allowing to select, for one or more sample IDs (which may be added or deleted), the target measurement unitsto be subjected for the inter-instrument difference evaluation and the one or more measurement items to be measured at the respective target measurement units. Here, in particular, the target sample with sample ID “” should be used to determine measurement data of the measurement items related to white blood counts (WBC), red blood counts (RBC), hemoglobin (HGB) and platelets (PLT) on each of the measurement unitshaving Instrument ID M, Mand M, for the purpose of the inter-instrument difference evaluation. Here, the measurement unitsmay be blood cell counting units for counting respective blood cells (WBC, RBC, PLT etc.) in a blood sample. Consequently, blood cell counts for the identical target sample can be determined at each of M, M, Mand these counts may be used to determine and evaluate an inter-instrument difference. The skilled person understands that additional or fewer instrument IDs, sample IDs, and/or measurement items can be selected, for example via the user interface.

160 110 160 160 In a case where a plurality of sample containers are transported to at least one of the measurement unitsby the sample transport device, the ID reader may be located at a transport start position of the sample transport device to read the IDs from the sample containers at the transport start position. In this case, the computermay identify the target sample at the transport start position based on the IDs read by the ID reader and control the transport device to transport the identified target sample to each of the target measurement unitswithout the need of the operator to manually transport the target sample to each of the target measurement units.

5 5 FIGS.A-C 110 160 160 160 According to an aspect of the present disclosure, especially represented by the processes of, the computerautomatically identifies the target sample used for measurement for the inter-instrument difference evaluation from a plurality of samples to be measured by at least one of the measurement units. Therefore, when the target sample is included among a plurality of samples routinely tested by at least one of the measurement units, the target sample can be automatically identified from the plurality of samples without operator intervention during the routine testing, and each of the target measurement unitscan be instructed to measure the target sample for the inter-instrument difference evaluation. This reduces the operator's burden of manually instructing each of the target measurement units to perform measurements on the target sample, thereby simplifying the operations for the inter-instrument difference evaluation.

110 114 160 116 6 FIG.A Preferably, the computerstores, in the storage device, sample identification information of the second sample (target sample) in association with each of the plurality of measurement results of the second sample obtained by measurements by the plurality of target measurement units.shows an exemplary data structure of the database. The measurement results of the target sample may be stored in this exemplary data structure which stores the measurement result (e.g., for WBC, . . . , PLT) in association with the ID of the sample and the Instrument ID. The exemplary data structure may also store a date and/or time as to when the measurement has been performed.

6 FIG.B 6 FIG.B 114 110 4 116 114 110 116 160 114 160 114 110 shows a process to generate evaluation information on the inter-instrument difference based on the measurement results stored in the storage device. In particular, when the inter-instrument difference evaluation is conducted, the computer, in step Sof, may search (interrogate) the databasefor a plurality of measurement results of the target sample (second sample). The storage deviceof the computermay store in the database, one or more measurement results of at least one first sample which has been measured, for example, for diagnosis of a test subject, by at least one of the plurality of the measurement units. The storage devicemay also store one or more sets of measurement results of at least one target sample (second sample) which has been measured, based on the measurement order including one or more preset measurement items for the inter-instrument difference evaluation, by each of the plurality of the target measurement units. In other words, the storage deviceof the computermay store a first measurement result of the first sample, which is obtained from measurement for diagnosis of the test subject by at least one of the plurality of the measurement units, and may also store a plurality of second measurement results of the second sample, which are obtained from measurements by the plurality of target measurement units.

114 The storage devicemay also store information such as data retrieval conditions for searching for the measurement results of the target sample. The data retrieval condition may be a condition of searching for the plurality of measurement results corresponding to the identified target sample. In other words, the data retrieval condition may be for identifying a set (bundle) of measurement results for the inter-instrument difference evaluation.

110 110 114 110 110 In order to generate the evaluation information, the computermay automatically search for the measurement results of the target sample according to the data retrieval conditions at a predetermined timing (e.g., per week, per month, per a few months, etc.). For example, in order to generate the evaluation information, the computermay interrogate the storage deviceto identify the set of the measurement results of the target sample based on the operator's instruction. For example, the operator may input search instruction to the computer, or may instruct the computerto perform the search (interrogation) according to the data retrieval conditions.

114 116 110 111 114 160 110 110 11 1 2 3 6 FIG.A 6 FIG.A In general, the storage device, in database, may store the measurement result of the first sample in association with first sample identification information of the first sample and store each of the measurement results of the second sample in association with second sample identification information of the second sample. The computerequipped with the processormay then autonomously search (interrogate), in order to generate the evaluation information, the storage devicefor the plurality of measurement results of the second sample. Each of the plurality of measurement results of the second sample is associated with the same ID (i.e., the ID of the second sample) and is obtained by different target measurement units. These measurement results, which match the data retrieval conditions, may be considered as the measurement results for the inter-instrument difference evaluation, and may serve as a source of the evaluation information. In other words, in order to generate the evaluation information, the computermay autonomously search for the measurement results obtained for the inter-instrument difference evaluation, and then generate the evaluation information based on the searched results. For example, regarding the exemplary data structure of, the computermay autonomously search for the measurement results (i) each corresponding to the same ID (in the, the ID “”) and (ii) each corresponding to different instrument IDs (IDs “M”, “M” and “M”).

110 116 110 110 5 FIG.C To search for the measurement results for generating the evaluation information, the computermay refer to the measurement items of the measurement results stored in the database. For example, the computermay autonomously search for the measurement results based on the data retrieval conditions such as (i) measurement results each corresponding to the same ID, (ii) measurement results each corresponding to different measurement units, and (iii) measurement results each corresponding to the same or common measurement items (i.e., for the inter-instrument difference evaluation, each result may be required to correspond to the same or common measurement items). Regarding the above mentioned (ii), it may be substituted with a condition such as “measurement results each corresponding to the designated target measurement units”. In this substitution, the computermay refer to the setting (as shown in) regarding the instrument IDs of the designated target measurement units.

110 110 110 110 11 1 2 3 116 110 6 FIG.A Based on such data retrieval conditions, the computermay be able to extract the measurement results that match the conditions and are considered as the source of the evaluation information. Based on the autonomous search (interrogation), the computermay also acquire multiple sets (bundles) of measurement results corresponding to multiple target samples. For each of the sets (bundles), the computermay generate the evaluation information. This way, the computermay search for a set (bundle) of measurement results of the target sample by using sample ID, measurement items and instrument ID as keys. The keys may also include Date/Time information to restrict a period to search for the measurement results of the target sample. For example, based on the Date/Time information, as illustrated in, it can be determined whether the measurement result of the ID “” has been obtained by each of the measurement instruments M, Mand Mwithin a certain pre-determined time window (period). This pre-determined time window may be set in order to identify a plurality of measurement results that should not be subject to the inter-instrument difference evaluation even if each of the plurality of measurement results is stored in association with (i) the same ID and (ii) different instrument ID of the target measurement unit. For example, if the databaseis configured to store measurement results over multiple days, the same ID may be associated with different samples in a facility where the same ID may be assigned to different samples on different days. In this case, if the pre-determined time window is set as “5 hours”, “10 hours”, etc., it is possible to identify a plurality of measurement results which are associated with the same ID but have been obtained over different days outside the time window. That is, if the measurement results are outside the pre-determined time window, the computermay exclude these measurement results from evaluating the inter-instrument difference.

115 115 The above are examples of conditions that may be used as a criterion (search information) for selecting or filtering out measurement results to be used to generate the evaluation information for the inter-instrument difference evaluation. Such data retrieval conditions may be coded in the (computer) program. For example, the programmay include codes to retrieve measurement results under the following conditions: (i) multiple measurement results each corresponding to the same ID (i.e., the ID of the sample), (ii) multiple measurement results each corresponding to different measurement units (i.e., different target measurement units), (iii) multiple measurement results corresponding to the same or common measurement items for the inter-instrument difference evaluation, and/or (iv) multiple measurement results within the pre-determined time window.

1 3 116 11 12 1 3 110 11 1 2 3 12 1 2 3 110 110 6 FIG.C 6 FIG.C 6 FIG.C Further, in an exemplary case where different target samples (e.g., two different target samples) have been measured by each of the target measurement units M-M, each of the plurality of measurement results of the target samples may be stored as a data structure in the databaseas shown in. In this case, the target samples have mutually different IDs (in the, “” and “”), and measurement results of each target sample have been obtained by each of the target measurement units M-Mfor the same or common measurement items. The computermay search for the plurality of measurement results corresponding to the ID “” and the instrument IDs “M”, “M” and “M” as a first set of measurement results, and the measurement results corresponding to the (different) ID “” and the instrument IDs “M”, “M” and “M” as a second set of measurement results. In other words, in this exemplary case, the computermakes groups of the searched measurement results according to the ID (i.e., the ID of the target sample). In the example shown in the, the first set of the measurement results belongs a group and the second set of the measurement results belongs another group. The computermay generate the evaluation information for each of the groups.

6 FIG.B 5 110 116 110 110 Referring back to, in step S, the computermay generate evaluation information for the inter-instrument difference evaluation based on or using the set of the measurement results of the target sample(s) (second sample) identified from the databaseof the computer. In particular, the computermay generate the evaluation information by comparing the identified set of measurement results to a reference or mean value, for example using statistical methods such as mean, standard deviation, coefficient of variation or acceptable bias to measure agreement or variation among target measurement units and output the evaluation information on the display.

7 FIG. 7 FIG. 7 FIG. 1 2 3 160 160 160 100 110 An example of the evaluation information is shown in. In this example, measurement values obtained by each of the target measurement units M, M, Mfor the target sample are combined in a comparable manner for each of the measured parameters (here, blood parameters: WBC, PLT, HGB, etc.), and a deviation (dev.) from a standard value for the inter-instrument difference evaluation is also included. In, a mean (average value) of the measurement values from the multiple target measurement unitsis used as the standard value. Instead of the mean of the measurement values from the multiple target measurement units, the measurement value by a master device may be used as the standard value. The master device may be one of the target measurement unitsthat belong to the sample analysis system. The deviation from the standard value may be automatically compared with an allowable range to evaluate the inter-instrument difference. The allowable range may be an acceptable limit within which the measurement value can vary from the standard value. When the allowable range is defined as 4% of the standard value as shown in, this means that the measurement value should not deviate more than 4% above or below the standard value. When the allowable range is expressed as the percentage, the computermay calculate a match rate indicating how well the measured value matches the standard value. The match rate m may be calculated based on the equation below:

110 where y is the measured value and x is the standard value. The computermay compare the calculated match rate with the allowable range.

7 FIG. 1 2 If the deviation is outside of the allowable range, a notification may be output and/or a control action may be performed. The control action may be an initiation of a cleaning operation, a suspension of operation of the measurement unit (and a corresponding re-routing of samples to other measurement units), and the like. As shown in, for example, deviations (“−0.3” for WBC in M, which corresponds to the match rate of approximately 4.5% and “0.5” for WBC in M, which corresponds to the match rate of approximately 7.5%) which are outside the allowable range may be displayed distinguishably from other values.

110 160 110 The computermay receive a designation of the master device from the multiple measurement units. The computermay receive a setting whether the mean (average value) of measurement values from the multiple target measurement units is used as the standard value or the measurement value by the master device is used as the standard value.

110 111 160 160 For example, when the computerequipped with the processoridentifies the plurality of measurement units to be subject for the inter-instrument difference evaluation, one measurement unit selected from the identified measurement unitsmay serve and may be set as the master device which may be used for obtaining the measurement result serving as the reference for the inter-instrument difference evaluation. The master device may be selected from the measurement unitsincluding the units designated for the inter-instrument difference evaluation and non-designated unit(s).

8 FIG. 8 FIG. 116 119 118 110 110 110 110 11 1 1 2 3 110 shows another example of the data structure of the database. In this example, the target sample used for measurement for the inter-instrument difference evaluation may be designated or selected by the operator via the operation deviceand/or the displayof the computer. The target sample may be designated or selected by inputting a measurement order for inter-instrument difference evaluation by the operator. The computermay autonomously designate the target sample. For example, the target sample may be randomly designated by the computer. An inter-instrument difference evaluation flag may be stored in association with the ID of the designated sample in the database. The computermay then search for measurement results of the target sample by using the flag as a key. This flag can be used as search information for searching for the measurement results of the target sample. In particular, as shown in, the target sample (having the ID “”) may be associated with the inter-instrument difference evaluation flag being set (e.g. to “”) to indicate that the set of measurement results obtained for the target sample at respective different measurement units M, M, Mmay be used for the inter-instrument difference evaluation. On the other hand, for other samples not used as the target samples for the purpose of inter-instrument difference evaluation, the inter-instrument difference evaluation flag is not set (e.g. to “0”). Consequently, the target sample and associated set of measurement results may be readily identified and assessed by the computer.

9 FIG. 9 FIG. 9 FIG. 116 1 2 110 1 1 1 2 110 110 116 160 12 2 1 12 2 116 114 110 1 11 1 3 11 1 11 shows another example of the data structure of the database. Such data structure may be advantageous in a situation where, for example, an initial measurement is conducted on the first sample by the measurement unit Mand re-measurement is conducted on the same sample by the measurement unit M. The computermay set a re-exam flag for the measurement result of the re-measurement. The re-measurement may occur for the same measurement items as the initial measurement, for example, when the measurement result obtained by the measurement unit Mhas an issue (e.g., the result has something questionable, the sample itself may have problem, the result may be unreliable, etc.). The re-measurement may also occur when the sample needs to be measured for additional measurement items that have not been measured at the initial measurement by the measurement unit M. In such cases, although the same sample with the same ID has been measured by multiple target measurement units Mand M, based on the data structure, the computermay advantageously be configured to not handle this sample as the target sample. The measurement result corresponding to the re-exam flag shown in theis not for the inter-instrument difference evaluation but just for the re-measurement because of the issue. The computermay not have to handle such sample as the target sample. Accordingly, this exemplary databasemay be configured so that the sample which has been measured by multiple target measurement unitsdue to re-measurement can easily be distinguished by the re-exam (re-examination) flag. For example, the sample of the ID “” measured by measurement unit Mis associated with re-exam flag “” which indicates that re-measurement on the sample of the ID “” was conducted by measurement unit Mand its measurement result is stored in the databaseof storage device. In this case, the computermay search for measurement results of the target sample from measurement results which are not associated with the re-exam flag “” (or in which the re-exam flag is not set). In, measurement results of a sample of the ID “” have been obtained by each of the target measurement units M-M, and the ID “” is not associated with re-exam flag “” in each of the associated Instrument IDs. The computer may then readily search for measurement results of the ID “” as measurement results of the target sample.

162 162 180 150 160 110 110 Instead of, or in addition to the re-exam flag, other information may be associated with the ID to exclude the sample from a scope of searching for measurement results of the target sample. For example, an error flag indicating a measurement error due to issues such as poor sensitivity of the detectoror deterioration of the staining solution for blood cells may be associated with the ID. This error may be detected, for example, using a hematological parameter reflecting the detector's sensitivity in detecting fluorescence from cells or reflecting the degree of staining of cells by the staining solution. As such parameter, for example, a median value of fluorescence intensities of all cells classified as neutrophils, which are the most common type of white blood cells, may be used. If this parameter value falls outside a preset numerical range, the measurement error may be detected. The data analysis unitof the analyzermay detect this error by analyzing the measurement data obtained by the measurement unit, and may send the error information in association with the corresponding measurement result to the computer. The computermay search for the measurement results for the inter-instrument difference evaluation so that the measurement results associated with the error flag are excluded from the search.

10 FIG. 6 FIG.C 6 FIG.B 110 11 110 116 110 110 11 12 110 162 12 110 110 13 110 5 110 12 110 14 14 110 shows an exemplary process of the computer. In this example, in step S, the computermay search for a set of measurement results of the target sample from the database. For example, the computermay search for the set of measurement results per target sample (i.e., per ID of the target sample). The computermay search for the set of measurement results corresponding to one ID (e.g., the ID “” as shown in the). In step S, the computermay determine whether measurement results of the target sample meet one or more conditions for performing the inter-instrument difference evaluation. The conditions may be for identifying reliable measurement results which are suitable to be used for the inter-instrument difference evaluation. For example, the conditions may require that the measurement results of the target sample has no issues such as poor sensitivity of the detector, deterioration of the staining solution for blood cells, or other problems (e.g., questionable results, potential issues with the sample itself, or unreliable results, etc.). The inter-instrument difference evaluation may have to be based on measurement results obtained without these issues. According to step S, the computermay be able to automatically discard measurement results with such issues and avoid using them for the inter-instrument difference evaluation. If the computerhas determined that measurement results of the target sample meet the conditions, in step S, the computermay generate the evaluation information from the searched set of measurement results corresponding to the ID in the same way as in step Sof. If the computerhas determined that measurement results of the target sample do not meet the conditions in step S, the computermay, in step S, search for another set of measurement results corresponding to a sample ID different from the ID which has been already searched. According to step S, the computermay repeat to search for the set of the measurement results until there is no remaining set of results for which the evaluation information has not been generated.

6 10 FIGS.A to 110 110 110 According to an exemplary aspect of the present disclosure, especially represented by the processes of, the computerautonomously searches for measurement results of the target sample from the database which stores measurement results of the target sample as well as measurement results of samples which have been measured for diagnosis of test subjects in routine sample measurements, and autonomously generates the evaluation information based on the measurement results of the target sample which have been searched from the database. That is, the computerinterrogates the database to identify the set of the measurement results of the target sample, which match conditions for use in the inter-instrument difference evaluation, and generates the evaluation information based on the identified set of the measurement results. Since the computeris able to autonomously perform operations for generating the inter-instrument difference evaluation, it is possible to reduce operator's workload for the inter-instrument difference evaluation.

150 160 180 180 110 In the above-explained embodiment, each analyzerincludes the measurement unitand the data analysis unit, and the data analysis unitis connected to the computer.

110 180 150 110 160 183 183 183 11 FIG. a b An embodiment may also be realized by a configuration in which the data analysis unit of one of the analyzers is utilized as the computer. That is, as shown in, the data analysis unit′ of one of the analyzersmay be utilized as the computerand be connected to each of the measurement units, and may have a function of receiving measurement data from each of all measurement units, processing the received measurement data using computer instructions in program (product)to generate the measurement results for each of the measurement units and storing the measurement results of samples measured by each of the measurement units in a corresponding databasein the storage device′.

160 110 116 110 1 183 180 1 2 183 180 2 110 110 In addition, instead of a configuration in which measurement results of samples which had been measured by each of the measurement unitsare collected by the computerand are centrally managed by the databasein the computer, the measurement results may also be stored in multiple databases via distributed management. For example, the measurement results of samples which had been measured by the measurement unit Mmay be stored in a database in the storage deviceof the data analysis unitcorresponding to the measurement unit M, and the measurement results of samples which had been measured by the measurement unit Mmay be stored in a database in the storage deviceof the data analysis unitcorresponding to the measurement unit M, and when the inter-instrument difference evaluation is conducted, the computermay access each of the databases and collect the measurement results of the target sample from each of the databases. According to this alternative embodiment, even if the databases are distributed across different devices, the computercan search the databases to automatically collect the measurement results of the target sample and generate the evaluation information, thus being able to reduce operator's workload when conducting inter-instrument difference evaluation.

12 FIG. 2 FIG. 3 4 FIGS.and 200 210 250 280 210 110 250 160 280 250 280 290 290 280 280 210 290 290 250 210 210 290 280 250 210 280 250 210 280 250 shows another sample analysis systemincluding a computer, a plurality of measurement unitscorresponding to respective analyzers, and a transport device. The configuration of the computercorresponds to the configuration of the computerdescribed above in conjunction with. In addition, the configuration of the measurement unitcorresponds to the configuration of the measurement unitdescribed above in conjunction with. The transport devicemay be configured to transport the sample container or a sample rack holding at least one sample container to at least one of the measurement units. The sample container may contain the target sample (second sample) or the first sample. The transport devicemay include an ID reader(identification information reader), such as the barcode reader, for reading the ID attached to the sample container. The ID readermay be located at the transport start position of the transport deviceto read the IDs from the sample containers at the transport start position. Operations of the transport devicemay be controlled by the computer, which may be communicatively connected to the ID reader. The ID readermay read ID of each of a plurality of first samples to be measured by at least one of the measurement units. This ID information may be then transmitted to the computer, and the computermay designate the second sample (target sample) from the plurality of first samples whose ID has been read by the ID reader. The transport devicemay transport the sample container of the target sample (second sample) to each of the plurality of target measurement unitswhich are subject for the inter-instrument difference evaluation. For example, the computermay autonomously designate the target sample from the plurality of first samples, and may control the transport deviceso that the designated target sample is transported to the target measurement units. The computermay not be just a single computer unit, but also be distributed computers or distributed computer units that may include a transport controller that controls the transport deviceand a measurement unit controller that controls the respective measurement units.

13 FIG. 13 FIG. 14 FIG. 14 FIG. 13 FIG. 13 FIG. 200 21 210 290 210 210 210 210 210 290 22 210 280 250 250 250 210 23 210 250 210 280 250 shows an exemplary process according to this sample analysis system. According to step Sof, the computermay autonomously identify (designate), by using one or more set conditions, the target sample from a plurality of the first samples whose ID has been read by the ID reader. For example, the computermay automatically designate the target sample based on a predetermined timing for conducting the measurements for the inter-instrument difference evaluation. As indicated inshowing a plurality of settable conditions on a schedule of the measurement for the inter-instrument difference evaluation, the predetermined timing may be preset and modified via the graphical user interface as exemplary shown in the. For example, the computermay receive the setting of intervals such as time periods. As the time period, the computermay receive settings such as once a year, one a month, every day, etc. If the setting of the interval is every day, for example, the computermay designate the first sample in each day as the target sample. For example, when the timing has arrived, the computermay randomly designate the target sample from the first samples whose ID has been read by the ID reader. Then, in step Sof, the computermay control the transport deviceto transport the designated target sample to each of the target measurement unitsfor the measurements for the inter-instrument difference evaluation. At each of the target measurement units, a portion of the target sample is aspirated and measured. The measurement results of the target sample obtained by the target measurement unitsare stored in the computer. Then, in step Sof, the computermay generate evaluation information based on the set of measurement results of the target sample measured by each of the target measurement units. Note that, for samples used for a routine measurement for diagnosis of test subjects, the computermay determine a destination measurement unit according to a measurement order of the sample for diagnosis of the test subject and may control the transport deviceto transport a sample container including the sample to the destination measurement unit.

21 200 210 250 161 210 In step S, if a condition on a quantity of the target sample has also been set in the sample analysis system, for example, the computermay also determine whether the sample container contains sufficient sample volume for the measurements by each of the target measurement units. The sample volume may be detected, for example, using an image sensor which captures a side view of the sample container. The captured image may be transmitted to the controller, which determines the liquid level through edge and contour detection of the image, then calculates the volume based on the container's geometry. If the sample volume does not meet the condition, the computermay identify a different sample as the target sample. This initial determination of a sufficient sample volume advantageously prevents termination of measurements for the purpose of inter-instrument difference evaluation due to insufficient sample volume.

21 210 290 210 210 200 In step S, the computermay designate, as the target sample, the sample whose measurement order includes measurement items which are suitable for the inter-instrument difference evaluation. For example, among a plurality of first samples whose ID has been read by the ID reader, if there is the sample whose measurement order for the diagnosis of the test subject includes measurement items which also cover measurement items for the inter-instrument difference evaluation, the computermay designate this sample as the target sample since the measurement result of the sample can also be utilized to the inter-instrument difference evaluation. If the measurement item of the measurement order can only be measured by a specific measurement unit, the computermay exclude such sample from being the target sample since such a sample is not suitable for the inter-instrument difference evaluation. For example, the systemmay include the specific measurement unit suitable for a specific measurement item, and there may be only one or a few of the specific measurement units. If a sample's measurement order includes only the specific measurement item, the sample is measurable only by the specific measurement unit. Thus, if such sample is designated as the target sample, the target measurement units may not be able to measure the sample. Therefore, such sample is not suitable for the inter-instrument difference evaluation.

13 FIG. 210 210 280 250 According to the process of, the computerautonomously designates the target sample, and the computercontrols the transport deviceso that the designated target sample is transported to each of the target measurement unitsfor inter-instrument difference evaluation. Therefore, automation can be further increased, and it is possible to further reduce operator's workload when performing measurement for inter-instrument difference evaluation.

210 250 210 15 FIG. The computermay additionally receive a setting of number of target samples. The number may be an integer greater than or equal to 2. If only a single target sample is measured by each of the target measurement units, measurement values of the single sample may fluctuate depending on which part of the sample within the sample container is aspirated for measurement, especially when the concentration of blood cells is unevenly distributed in the sample. In order to reduce the impact of the fluctuations on measurement result to be used for the inter-instrument difference evaluation, the computermay be configured to receive a setting of the number of target samples N to, for example, obtain an average value of the total measurement values for the N target samples. The operator may enter the number of target samples N such as 20 for statistical calculation through a setting screen of a graphical user interface, as shown in. The skilled person understands that this improves the accuracy of the inter-instrument difference evaluation. The number of target samples N may be fixed at a default value.

16 FIG. 16 FIG. 16 FIG. 16 FIG. 210 21 210 290 22 210 280 250 250 210 23 210 shows a process to generate evaluation information when the computerhas received the setting of number of target samples N. In step SA of, for example, the computermay identify N target samples from a plurality of first samples whose ID has been read by the ID reader. Then, in step SA of, the computermay control the transport deviceto transport each of the identified N target samples to each of the target measurement unitsfor measurement for the inter-instrument difference evaluation. At each of the target measurement units, each of N target samples is aspirated by the target measurement unit and measurement of each target sample is conducted. The measurement results of each of the N target samples are stored in the computer. Then, in step SA of, the computermay generate evaluation information by statistically calculating measurement values of the N target samples.

17 FIG. 1 3 1 210 For example, evaluation information may be output as shown infor each measurement item. While this example is described for the measurement item WBC when N (number of target samples) is 20, the skilled person understands that the evaluation information may equally be provided for other measurement items and/or for different number of target samples N. In this example, a precision rate and a regression coefficient may be statistically calculated for each of the target measurement units M-M. When the calculated value is outside an allowable range, an indication such as an error mark may be displayed. For example, since the precision rate of the measurement unit Mis 89% which is below a threshold value 90%, the exclamation mark (“!”) is added at the display area of the precision rate 89%. The precision rate and the regression coefficient may be calculated by the computeras follows:

210 (1) For each target sample, the computermay calculate the match rate indicating how well the measured value by each target measurement unit matches the standard value. The match rate m may be calculated based on the equation below:

where y is the measured value by each target measurement unit and x is the standard value. x may be the measured value by the master device, or x may be an average of measured values obtained by each of the target measurement units.

210 (2) For each of the target measurement units, the computermay count the number of target samples whose match rate is within an allowable range, and the counted number is represented as G.

210 (3) For each of the target measurement units, the computermay calculate a ratio between the G and N and obtain the precision rate P based on the equation below:

If the precision rate P is greater than or equal to a threshold value such as 90%, the target measurement unit is determined to pass the inter-instrument difference evaluation.

200 210 When the master device has been set in the sample analysis system, the computermay calculate master device average, measurement unit average, standard deviation, and covariance using the following formula.

1 N 1 N x y xy where x, . . . , xare the measured values of the master device; y, . . . , yare the measured values of the target measurement unit other than the master device; SDis the standard deviation of the master device; SDis the standard deviation of the target measurement unit other than the master device; Cis the covariance.

210 The computermay calculate a correlation coefficient using the following formula based on the covariance and standard deviation.

210 The computermay calculate the regression coefficient using the following formula based on the correlation coefficient and standard deviation.

where a is the regression coefficient and r is the correlation coefficient.

200 210 1 N When the master device has not been set in the sample analysis system, the computermay calculate an average of the measurement values from each of the target measurement units and set the average values as x, . . . , x.

210 210 210 250 200 250 210 In the configuration where the computeridentifies the N target samples to generate the evaluation information, the computermay selectively identify the N target samples which possess a specific attribute. This attribute may refer to a specific characteristic or property of the sample. The computermay be configured to distinguish the attribute of each target sample based on a measurement result of the target sample which has been already measured by at least one of the measurement unitsfor diagnosis of a test subject. That is, this configuration is based on the sample analysis systemwhere the target sample is selected from a plurality of first samples after they have been measured by at least one of the measurement units. One such attribute may be a cell concentration indicating a blood cell concentration of the target sample. For example, the computermay selectively identify the N target samples with low cell concentration (below a first threshold). The cell concentration used as the attribute may not only be low but also middle (between the first threshold and a second threshold) or high (above the second threshold). The specific attribute for selectively identifying the N target samples may be information indicating whether a normal or abnormal measurement value has been obtained, or whether an abnormal feature has been detected as a result of the measurement.

18 FIG. 19 FIG. 19 FIG. 300 350 1 2 350 380 310 310 350 350 350 350 310 310 380 1 350 1 2 350 3 3 350 2 310 350 350 350 350 310 In a facility with a plurality of measurement units such as dozens of measurement units, it may be impractical to conduct the inter-instrument difference evaluation measurement using a single sample container for all the target measurement units in the facility. To address this issue, the computer may be configured to control a sample analysis system so that the deviation of each target measurement unit relative to a master device can be calculated, allowing the inter-instrument difference among all the target measurement units to be evaluated based on these calculated deviations.illustrates an example of a sample analysis systemincluding a master device (which is a master measurement unit)′ and additional measurement units,, . . . , M, all indicated with reference sign, which may be serviced by a transport devicewhich may be controlled by the computeras described above. In this embodiment, the computermay generate a plurality of groups, each including the master device′ and one or more target measurement units. The number of the measurement units in each group is preferably limited to a number that can be covered by the single sample container.shows an example of the groups, each including the master device′ and another measurement unitas a pair. The computermay allocate each of different target samples to each of the groups so that the measurement units in the same group can measure the same target sample. Then, the computermay control the transport deviceso that each target sample is transported to each of the measurement units in each group and measured for evaluation of inter-instrument difference in each group. According to the example shown in, a first target samplemay be allocated and measured for evaluation of inter-instrument difference between the master device′ and measurement unit, a second target samplemay be allocated and measured for evaluation of inter-instrument difference between the master device′ and measurement unit, a third target samplemay be allocated and measured for evaluation of inter-instrument difference between the master device′ and measurement unit. The computermay then calculate the difference of measurement results between the master device′ and the corresponding one or more measurement unitsin each group to evaluate whether the measurement units in each group can demonstrate equivalent measurement performance. If the difference of measurement results between the master device′ and the corresponding one or more measurement unitsin each group is within an allowable range, the computermay determine that all of the target measurement units can produce equivalent measurement results.

350 350 310 350 350 19 FIG. Instead of generating the group including the master device′ and other measurement unitas a pair as illustrated in, the computermay generate a plurality of groups, each including the master device′ and other two or more measurement units.

18 FIG. 19 FIG. 350 350 350 350 According to the alternative embodiments shown byand, even if the number of the target measurement unitsmakes it impractical to perform the measurement for inter-instrument difference evaluation using a single sample container for all the target measurement units, it is possible to perform measurements for evaluating the inter-instrument difference among all the target measurement unitswithout requiring an operator to perform tasks such as picking up a plurality of target samples, dividing the target measurement unitsinto groups, allocating each target sample to a group and manually transporting each target sample to respective groups.

20 FIG. 1 1 717 In this embodiment of the present disclosure, a label including a unique identifier for uniquely indicating a sample for the measurement for the inter-instrument difference evaluation may be attached onto a sample container containing the target sample so that the sample analysis system can automatically identify the target sample. For example, as shown in, a label BLmay be attached onto the sample container T containing the target sample. The label BLmay include, as the unique identifier, a special sample ID specifically for the measurement for the inter-instrument difference evaluation. The special sample ID may be created by combining predetermined set of letters, such as “PSC”, with a sample ID number of the target sample. The unique identifier does not have to be special. For example, a specific set of last three digits of the ID (e.g., “”) may be preset as the unique identifier in the computer. If the ID of the sample read by the ID reader of the sample analysis system includes the last three digits corresponding to the preset values, the sample may be recognized as the target sample. The preset values may be determined according to the facility's ID assignment rules and may include a combination of letters and numbers.

21 FIG. 12 FIG. 200 101 290 280 210 290 102 210 210 103 280 250 210 250 250 210 290 102 210 280 250 104 104 210 210 250 250 280 250 210 250 105 116 210 116 shows an exemplary process of this embodiment based on the sample analysis systemshown in. In step S, the ID may be read by the ID readerfrom a label of a sample container at the transport start position of the transport device. If the computerhas determined that the ID read by the ID readerincludes the unique identifier in step S, the computermay determine that the timing to conduct measurement for the inter-instrument difference evaluation has arrived, and the computermay identify the sample in the sample container as the target sample and, in step S, may control the transport deviceto transport the sample container to each of the target measurement units. The computermay read out the measurement order including the preset one or more measurement items for the inter-instrument difference evaluation and transmit it to each of the target measurement units. At each of the target measurement units, a portion of the same target sample may be aspirated, and preparation of measurement samples and measurement for the same measurement items are conducted. On the other hand, if the computerhas determined that the sample ID read by the ID readerdoes not include the unique identifier in step S, the computermay control the transport deviceto transport the sample container to at least one of the measurement unitsin step S. In step S, the computermay read out this sample's measurement order that has been registered for diagnosis of a patient. Then, the computermay determine a destination measurement unitbased on the measurement order of the sample, availability information of each measurement unit, etc., and may control the transport deviceto transport the sample container to the destination measurement unit. The computermay transmit the measurement order to the destination measurement unitso that the measurement of the sample is conducted according to the measurement order. Then, in step S, the measurement result of the measured sample is stored in databaseof the computerin association with the ID and Instrument ID. Here, the measurement results of the target sample are stored in the databasein association with the sample ID including the unique identifier.

22 FIG. 116 12 11 210 11 1 2 3 shows an exemplary data structure of the databasein which measurement results are stored in association with the ID and Instrument ID. The measurement results obtained by routine measurements for diagnosis of patients are stored in association with the ID which is a regular format such as “”. The measurement results obtained by measurement for the inter-instrument difference evaluation are stored in association with the ID including the unique identifier such as “PSC”. When generating the evaluation information, the computermay search for measurement results of the target sample corresponding to the unique identifier “PSC” and Instrument IDs “M”, “M” and “M”. This unique identifier can be used as search information for searching for the measurement results of the target sample.

210 290 280 280 250 According to this embodiment, the computeridentifies the target sample based on the ID read by the ID readerat the transport device, and controls the transport deviceto transport the identified target sample to each of the target measurement units. Therefore, it is possible to automatically perform measurement for the inter-instrument difference evaluation simply by placing the sample container with unique identification information onto the transport device. This reduces the need for operator intervention.

200 210 101 210 290 102 290 210 103 250 The sample analysis systemmay also be utilized in a case where the ID of the target sample is designated by the operator and the designated ID is stored in the storage device of the computer. In this embodiment, in step S, the computermay receive the ID read by the ID readerfrom a sample container, and in step S, may determine whether the ID read by the ID readermatches the ID designated by the operator as the target sample. When the IDs match, the computermay identify the target sample, and in step S, may transport the sample container to each of the target measurement unitsfor measurement for inter-instrument difference evaluation.

23 FIG. 2 55 A label including the unique identifier may be attached onto a sample rack which can hold one or more sample containers.shows an example of the sample rack having a label BLincluding, as the unique identifier, a special rack ID specifically for the measurement for the inter-instrument difference evaluation. The special rack ID may include a predetermined set of letters such as “PSCR”. Alternatively, the unique identifier does not have to be special. For example, a specific set of last two digits of a rack ID (e.g., “”) may be preset as the unique identifier in the computer.

24 FIG. 12 FIG. 200 201 280 290 290 210 290 202 210 210 203 210 280 250 210 250 250 210 290 202 210 280 250 204 204 210 210 250 250 280 250 210 250 205 116 210 116 shows an exemplary process based on the sample analysis systemshown in. In step S, at the transport start position of the transport device, the rack ID may be read from a label of a sample rack by the ID readerand the ID of the sample may be read from a label of each sample container in the sample rack by the ID reader. If the computerhas determined that the rack ID read by the ID readerincludes the unique identifier in step S, the computermay determine that the timing to conduct measurement for the inter-instrument difference evaluation has arrived, and the computermay identify each sample in the sample rack as the target sample and, in step S, the computermay control the transport deviceto transport the sample rack to each of the target measurement units. The computermay read out the measurement order including a preset one or more measurement items for the inter-instrument difference evaluation and transmit it to each of the target measurement units. At each of the target measurement units, a portion of the target sample contained in each sample container in the sample rack may be aspirated, and preparation of measurement samples and measurement for the same measurement items are conducted according to the measurement order. On the other hand, if the computerhas determined that the rack ID read by the ID readerdoes not include the unique identifier in step S, the computermay control the transport deviceto transport the sample rack to at least one of the measurement unitsin step S. In step S, the computermay, for each sample in the sample rack, read out a measurement order that has been registered for diagnosis of a patient. Then, the computermay determine a destination measurement unitbased on the measurement order of each sample, availability information of each measurement unit, etc., and may control the transport deviceto transport the sample rack to the destination measurement unit. The computermay transmit the measurement order for each sample to the measurement unitso that each sample in the sample rack is measured according to the measurement order. Then, in step S, the measurement result of the measured sample is stored in databaseof the computerin association with the ID of the sample, the rack ID and the Instrument ID. The measurement results of the target sample are stored in the databasein association with the rack ID including the unique identifier.

25 FIG. 116 2 3 210 1 2 3 shows an exemplary data structure of the databasein which measurement results are stored in association with the ID of the sample, the rack ID and the Instrument ID. The measurement results obtained by routine measurements for diagnosis of patients are stored in association with the ID and the rack ID which are defined with the regular form such as “R” or “R”. The measurement results obtained by measurement for the inter-instrument difference evaluation are stored in association with the rack ID including the unique identifier such as “PSCR”. To generate the evaluation information, the computermay search for a set of measurement results of the target sample corresponding to the unique identifier “PSCR” and the Instrument IDs “M”, “M” and “M”.

210 290 280 280 250 According to this embodiment, the computeridentifies one or more target samples based on rack identification information read by the ID readerat the transport device, and controls the transport deviceto transport the sample rack holding the identified one or more target samples to each of the target measurement units. Therefore, it is possible to automatically perform measurement of one or more samples for the inter-instrument difference evaluation simply by placing the sample rack with unique identification information onto the transport device. This reduces the need for operator intervention.

200 210 201 210 290 202 210 290 210 203 250 The sample analysis systemmay also be utilized in a case where the rack ID of the sample rack for holding one or more target samples is designated and the designated rack ID is stored in the storage device of the computer. In this embodiment, in step S, the computermay receive the rack ID read by the ID readerfrom a sample rack, and in step S, the computermay determine whether the rack ID read by the ID readermatches the designated rack ID. When the rack IDs match, the computermay identify the one or more target samples in the sample rack, and in step S, may transport the sample rack to each of the target measurement unitsfor measurement for inter-instrument difference evaluation.

161 161 Other unique information instead of the above-explained unique identifier may also be used to distinguish the sample rack corresponding to the inter-instrument difference evaluation measurement. The unique information may be color information of a unique color which indicates that the rack is used for a measurement for the inter-instrument difference evaluation. The unique color may be different from a color of a normal rack for routine measurements for diagnosis of patients. The color information of the unique color may be pre-set in the computer. In this alternative approach, when conducting the measurement for the inter-instrument difference evaluation, an operator may place one or more sample containers, each containing the target sample, into the sample rack with the unique color and may place this sample rack at the transport start position of the transport device. In order to detect the color of the sample rack, the transport device may include, at the transport start position, an image sensor which is configured to capture an image of a predefined region of the sample rack. The captured image may be transmitted to the controller, which analyzes the image and extracts the color components of the image pixels. The controllermay obtain average values of the red (R), green (G) and blue (B) color values of the pixels and identify the color of the sample rack by comparing these average values with reference data values. The transport device may include a color sensor configured to detect the color of the sample rack. The color sensor emits light from a light emitter to the sample rack and then receives light reflected back from the sample rack with a light receiver. The color sensor may measure the intensity of the reflected light for each of red, green and blue wavelengths, calculate a ratio of the intensities of the red, blue and green light, and identify the color of the sample rack by comparing the calculated ratio with reference ratios. The detection result of the color of the sample rack may be transmitted to the computer, which then determines whether the color of the sample rack corresponds to the unique color. When the computer has determined that the color of the sample rack matches the unique color, the computer may identify each sample in the sample rack as the target sample and control the transport device to transport the sample rack to each of the target measurement units. When measurement results of the target sample are obtained by each of the target measurement units, the measurement results are stored in database of the computer in association with a flag indicating the unique color, the ID of the sample and the instrument ID so that the computer can search for measurement results corresponding to the flag from the database.

1 Alternatively, instead of using the transport device, the sample container containing the target sample may be manually transported to each of the target measurement units by the operator. The operator may pick up a sample container which contains the sample suitable for conducting measurement for the inter-instrument difference evaluation by observing a color or volume of the sample. The operator may attach the label including the unique identifier, such as the label BL, onto the sample container and then manually transport the sample container to each of target measurement units that are subject to the inter-instrument difference evaluation.

165 116 At each of target measurement units, the ID including the unique identifier may be read from the label of the sample container by the ID readerand the sample ID may be transmitted to the computer. The computer may identify the target sample based on the unique identifier and transmit the measurement order for the measurement for the inter-instrument difference evaluation to each of the target measurement units so that the target sample is measured by each of the target measurement units for one or more same/common measurement items. The measurement results obtained based on measurements by each of the target measurement units may be stored in databaseof the computer in association with the ID including the unique identifier.

2 The sample rack holding one or more target samples may be manually transported to each of the target measurement units by the operator. The operator may pick up one or more sample containers, each containing the sample suitable for conducting measurement for the inter-instrument difference evaluation, place the picked-up one or more sample containers in the sample rack having the label including the unique identifier, such as the rack label BL, and then manually transport the sample rack to each of the target measurement units.

165 165 At each of the target measurement units, the rack ID including the unique identifier may be read from the label of the sample rack by the ID readerand a sample ID may be read from each sample container in the sample rack by the ID reader. These IDs may be transmitted to the computer. The computer may identify each sample in the sample rack as the target sample based on the unique identifier included in in the rack ID and transmit the measurement order for the measurement for inter-instrument difference evaluation to each of the target measurement units so that each target sample in the sample rack is measured by each of the target measurement units for one or more same/common measurement items.

116 The measurement results obtained based on measurements by each of the target measurement units may be stored in databaseof the computer in association with the rack ID including the unique identifier.

400 500 26 FIG. 27 FIG. The present disclosure related to the transport device may further be exemplified by the configuration of a sample analysis systemas shown inor the configuration of a sample analysis systemas shown in.

26 FIG. 400 450 450 450 400 In the configuration as shown in, the sample analysis systemmay include multiple measurement unitsbeing adjacently arranged along a single transport device. The transport device may include: a rack placement section where a sample rack is placed by the operator; a transport line that receives the sample rack from the rack placement section and transports the sample rack to at least one of the multiple measurement unitsthat are arranged along the transport line; and a rack receiving section that receives the sample rack from the transport line. The transport device may be equipped with an ID reader which reads ID before the sample container is transported to any of the measurement units. The computermay control operations of the transport device and the measurement units based on the ID read by the ID reader.

500 550 580 580 581 580 581 580 560 581 580 582 580 580 581 582 510 510 510 560 510 510 500 580 550 27 FIG. 27 FIG. a b b a In the configuration of the sample analysis systemas shown in, multiple measurement unitsand multiple transport devicesmay be arranged in one-to-one correspondence. The multiple transport devicesare connected to each other. A rack loading devicemay be arranged in an upstream side of the transport devices. Sample racks may be placed by the operator onto the rack loading deviceand may be loaded by the rack loading device onto the transport deviceon the upstream side. ID readermay be installed in the rack loading device so that the ID can be read before the sample racks are loaded from the rack loading deviceinto the transport device. A rack collecting devicemay be arranged in a downstream side of the transport devices. Operations of the multiple transport devices, the rack loading deviceand the rack collecting devicemay be controlled by the computer(a main controllerand a transport controller) based on the ID read by the ID reader. The transport operations may be controlled by the transport controllerand the measurement operations may be controlled by the main controller. As further indicated in, a sample rack may include a plurality of samples including at least one target sample, and the sample analysis systemmay be controlled to transport the at least one target sample via the multiple transport devicesto each of the multiple measurement unitsfor the purpose of evaluating the inter-instrument difference.

110 210 310 410 510 110 210 310 410 510 150 250 350 450 550 616 614 614 615 28 FIG. In this embodiment of the present disclosure, the computer,,,,may automatically designate the target sample suitable for the measurement for the inter-instrument difference evaluation, based on or using measurement results of a plurality of samples which have already been measured by at least one of the measurement units. That is, the computer,,,,may designate the target sample from samples which have been measured by at least one of the measurement units. In other words, the computer may designate, as the second sample (target sample), one of a plurality of the first samples that have already been measured by at least one of the plurality of the measurement units. For example, the computer may designate the target sample according to the measurement result of the first sample that has already been measured by at least one of the plurality of measurement units,,,,. In particular, the the target sample may be designated by selecting the first sample whose measurement result meets one or more selection criteria. As shown in, the one or more selection criteria may be stored in the databaseof the storage deviceof the computer. The storage deviceof the computer may also store a program (product). The one or more selection criteria may be stored as an exemplary form of criteria table, for example in the form of a data structure or the like.

29 FIG. 29 FIG. 29 FIG. 1 2 3 4 shows an exemplary criteria table indicating examples of the one or more selection criteria. As shown in, the criteria table may store defined criteria, including a range of values. The range of values may indicate anormal value range so that normal samples can be selected as the target samples. Conversely, the range of values may indicate an abnormal value range so that abnormal samples can be selected as the target samples. This allows the operator to verify whether the target measurement units can equivalently measure the abnormal samples and produce measurement results within the abnormal value range. The criteria may also include one or more messages and/or one or more alert flags that may be produced as a result of the measurement. By selecting the abnormal samples that meet the criteria, the operator is able to verify whether the target measurement units can equivalently measure these abnormal samples and produce the same messages or alert flags. The criteria table may also include additional various criteria. In the exemplary criteria table of, the criteria of ID “” is defined for identifying samples whose measurement results (here, with regard to WBC, PLT, HGB) are within normal value ranges, the criteria of ID “” is defined for identifying samples whose measurement results are within abnormal value ranges, the criteria of ID “” is defined for identifying samples whose measurement results have triggered the message representing specific measurement result such as “NRBC present”, and the criteria of ID “” is defined for identifying samples whose measurement results have triggered the alert flag. The message “NRBC present” may be produced if NRBC (Nucleated Red Blood cells) values or percent valued thereof exceed a threshold. The alert flag may be produced if the measurement results are suspicious. The criteria may also include messages or alert flags related to immature granulocytes, primitive cells, anemia, iron deficiency anemia, trilineage reduction, thrombocytopenia, thrombocytosis, etc. The skilled person understands that these are non-limiting examples of the one or more selection criteria.

100 200 300 400 500 30 FIG. The selection criteria may be set by the operator of the sample analysis system,,,,. As shown inindicating an exemplary graphical user interface for setting the selection criteria, the operator may set a parameter by selecting, from a drop-down list, e.g. “WBC” in the field of parameter, may further define one or more logical operators by selecting, from a drop-down list, including a plurality of logical operators such as {>, ≥, <, ≤, =}, e.g. “<”, and may enter (numerical) value, e.g. 10, in the field of value. The physical unit defined for the parameter may also be displayed automatically in the field of unit.

30 FIG. 31 32 FIGS.and The operator may be able to add a new line, via the exemplary graphical user interface, to combine the multiple parameters.shows that four parameters may be combined to set a single criterium. As further shown in, the operator may also set (“ON”) or unset (“OFF”) messages and flags as additional criteria. For example, if the measurement result has the message which is set to “ON” as the criteria, the computer may select the sample corresponding to the result having such message.

110 210 310 410 510 110 210 310 410 510 616 33 FIG. 8 FIG. For example, if the computer (,,,,) has determined that a timing (e.g., the timing arriving in a predetermined frequency such as per day, per few days, per week, per few weeks, per month, per few months, etc.) to conduct the inter-instrument difference evaluation has arrived, the computer may autonomously/automatically select the target sample by applying the selection criteria to the measurement results stored in the database of the computer. For example, if the computer (,,,,) has received an instruction from the operator to conduct the inter-instrument difference evaluation, the computer may initiate to compare the criteria and the measurement results measured after receiving the operator's instruction. If the computer finds that the measurement result matches the criteria, the computer may designate the first sample corresponding to the matched result as the target sample.shows a list of the selected target samples which may be displayed by the computer. The displayed information may include sample IDs of the selected target samples and/or the criteria IDs used for selecting the samples. The computer may store flag information indicating the inter-instrument difference evaluation in association with a sample ID of the selected sample in the database, as illustrated in.

In an exemplified case where the selected sample is placed on a transport device, a sample ID of the selected sample may be read by an ID reader located at or near the transport device and the computer may identify the selected sample as the target sample by comparing the sample ID read by the ID reader and the sample ID which is stored in association with the flag information. The computer may then control a transport of the identified target samples to each of the target measurement units by the transport device and send measurement instructions to each of the target measurement units to conduct the (same) measurement for inter-instrument difference evaluation.

33 FIG. In another exemplified case, the operator may refer to a display showing the list ofand attach a label including the unique identifier to the sample container(s) containing the selected samples, or place the sample containers containing the selected samples into the sample rack onto which a label including the unique identifier is attached. When these samples or rack are placed on a transport device, the computer may identify the target sample based on the unique identifier which is read by ID reader located at the transport device.

According to this embodiment, the computer autonomously/automatically selects or searches for a sample suitable for the measurement for inter-instrument difference evaluation, based on the measurement result of the first sample and the selection criteria. This reduces the operator's workload for designating the target sample.

110 210 310 410 510 116 51 52 116 53 20 34 FIG. 34 FIG. In this embodiment of the present disclosure, the computer,,,,may generate a report as the evaluation information based on the measurement results stored in the database. This report may evaluate the equivalency of measurement results among multiple measurement units in a facility and may be used to document results of periodic evaluations of inter-instrument differences.shows a process to generate and output the report. In particular, as shown in the flowchart of, the computer, in step S, may determine whether an operator's instruction to output a report has been received. The computer may be configured to receive the instruction together with a designation of a target time period. When the operator wants to refer to measurement results of one or more target samples which were measured on a date such as 2024 Mar. 13, the operator can designate this date as the target time period. The computer may also be configured to receive the designation of time period of more than 1 day by receiving a starting date and an end date. Then, in step S, the computer may search the databasefor at least one set of measurement results of the one or more target samples within the designated time period. Then, in step S, the computer may generate the report based on these retrieved measurement results and output the report. Instead of the time period, the computer may also be configured to receive the designation of the number of the target samples such as “” to identify the designated number of the target samples going back from the current time.

35 FIG. 35 FIG. 35 FIG. 35 FIG. 35 FIG. 1 2 3 1 1 shows an example report for the inter-instrument difference evaluation. As shown in, the generated report may include the designated time period (here: 2024 Mar. 31) and target measurement units (here: M, M, M). The target measurement units are measurement units which were set as the target measurement units in the facility during the designated time period. Additionally, the report may also include the number of target samples that were measured during the designated time period. As shown in, the report may include sections for presenting overall evaluation results and detailed results. The overall evaluation section may include determination results and determination conditions for each measurement item of the preset one or more measurement items for the inter-instrument difference evaluation. The determination conditions are for evaluating whether measurement results from the respective target measurement units are equivalent to each other. The computer may determine a valid or acceptable inter-instrument difference (“OK”) if measurement results of all target measurement units meet the determination conditions, and may determine an invalid or unacceptable inter-instrument difference (“NG”) if measurement results of at least one of the target measurement units fail to meet the determination conditions. In the example shown in, the computer has determined “OK” for PLT measurements since measurement results of all target measurement units meet the determination conditions (Allowable range: +−3%, Precision rate: 90≤p). However, for WBC measurements, the computer has determined “NG” since measurement results of at least one target measurement unit do not meet the determination conditions (Allowable range: +−4%, Precision rate: 90≤p). When the determination result is “NG”, the operator can identify which measurement unit has caused this result by examining the details section of the report. In the example shown in, the operator can identify the measurement unit Mas the cause of the “NG” result for WBC measurement item, as the WBC result from the measurement unit Mis highlighted in the details section due to the precision rate of 89%, which does not meet the required condition of “Precision rate: 90≤p”.

The operator may conduct a calibration of the measurement unit whose measurement result had violated the determination conditions and re-conduct measurement for the inter-instrument difference evaluation after the calibration of the measurement unit.

In the foregoing detailed description of the present disclosure, reference is made to the accompanying drawings that form a par thereof, and in which is shown by way of illustration how examples of the disclosure may be practiced. These examples are described in sufficient detail to enable those of ordinary skill in the art to practice the examples of this disclosure, and it is to be understood that other examples may be utilized and that process, electrical, and/or structural changes may be made without departing from the scope of the present disclosure.

Elements shown in the various figures herein can be added, exchanged, and/or eliminated so as to provide a number of additional examples of the present disclosure. In addition, the proportion and the relative scale of the elements provided in the figures are intended to illustrate the examples of the present disclosure and should not be taken in a limiting sense.